Abstract 9679: Fast/Glycolytic Skeletal Muscle Growth Attenuates Cardiac Dysfunction and Remodeling After Experimental Myocardial Infarction
Introduction: It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). In contrast, little is known about the effect of resistance exercise on these processes, partly because animal models that can assess the relationship between glycolytic muscle fiber growth and cardiac remodeling have been lacking.
Hypothesis: Fast/glycolytic skeletal muscle growth attenuates cardiac dysfunction and remodeling after MI.
Methods: We utilized skeletal muscle-specific, conditional Akt1 transgenic (TG) mice, that can induce the growth of functional fast/glycolytic skeletal muscle by switching Akt1 signaling on in muscle fibers. Male non-induced TG mice and their non-transgenic littermates (control) were subjected to left anterior descending coronary artery ligation. Two days after surgery, mice were provided doxycycline in their drinking water to activate Akt1 transgene expression in a skeletal muscle-specific manner. Cardiac function and remodeling were assessed by micromanometer catheter, echocardiography, histology and gene expression analyses at 2 and 4 weeks after surgery.
Results: Activation of Akt1 signaling in myofibers led to a modest increase in skeletal muscle mass. Skeletal muscle-specific activation of Akt1 led to diminished left ventricular dilation and reduced contractile dysfunction compared with control mice at 4 weeks after MI. The increase in heart weight/BW ratio and lung wet weight/BW ratio was significantly diminished in Akt1 TG mice compared to control mice, consistent with an improvement in heart function. Improved cardiac function in Akt1 TG mice was coupled to diminished myocyte hypertrophy, decreased interstitial fibrosis in the infarct border zone, and increased capillary density in the remote zone. Comprehensive protein array analysis showed that panels of angiogenic factors were increased in skeletal muscle in TG mice. An ELISA analysis demonstrated that serum VEGF levels were upregulated in Akt1 TG mice compared with control mice.
Conclusions: Akt1-mediated skeletal muscle growth attenuates cardiac remodeling after MI, and this is associated with increased capillary density in the heart and a reduction in cardiac fibrosis.
- © 2011 by American Heart Association, Inc.